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K Mattson

Publications and source records attributed to K Mattson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma.

Besides asbestos exposure, the factors that determine susceptibility to malignant mesothelioma are unknown. We evaluated the risk of GSTM1 null genotype and slow acetylation-associated NAT2 genotype for malignant mesothelioma in relation to asbestos exposure. Both the GSTM1 null genotype and the NAT2 slow acetylator genotype placed individuals at about 2-fold increased risk of developing malignant mesothelioma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0-3.5 and OR = 2.1, 95% CI = 1.1-4.1, for the GSTM1 and NAT2 genes, respectively]. When the patients were divided into low/moderate and high exposure groups according to their asbestos exposure histories, the effect of the at-risk genotypes was mostly attributable to the high exposure groups (OR = 2.3, 95% CI = 1.0-5.6 and OR = 3.7, 95% CI = 1.3-10.2, for the GSTM1 and NAT2 genes, respectively). The individuals with combined GSTM1 and NAT2 defects had about a 4-fold risk of developing malignant mesothelioma compared to those with the GSTM1 gene and NAT2 fast acetylator genotype (OR = 3.6; 95% CI = 1.3-9.6). Moreover, the risk among subjects highly exposed to asbestos with the double at-risk genotype was more than 7-fold greater compared to those with the more beneficial genotypes of both GSTM1 and NAT2 genes (OR = 7.4; 95% CI = 1.6-34.0).

Adult↗
PubMed1995

Inhaled recombinant interferon gamma in patients with lung cancer: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages and peripheral blood neutrophils and monocytes.

PURPOSE: A Phase I trial was conducted to investigate clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AM) and peripheral blood neutrophils and monocytes after inhalation of recombinant interferon (r IFN)-gamma. METHODS AND MATERIALS: Eight patients with lung cancer inhaled r IFN-gamma as single doses of 0.1, 0.2, 0.6, 1.8, or 5.4 mg. Bronchoalveolar lavage was performed three times, 21 h before as well as 3 and 27 h after inhalation. RESULTS: Interferon-gamma was detectable in bronchoalveolar lavage fluid (BALF) samples taken 3 h after inhalation in doses of > or = 0.6 mg. Before inhalation, AM in four out of seven patients studied showed vigorous lucigenin-enhanced CL responses to N-formyl-methionyl-leucyl-phenylalanine and opsonized zymosan particles. Furthermore, the responses were markedly increased 3 h after inhalation. In three out of seven patients, AM in the pretreatment BALF samples showed low or no CL responses, and the responses did not increase after inhalation of IFN-gamma, suggesting that the patients were anergic. Postinhalation CL responses did not correlate with the dose of IFN-gamma inhaled. Circulating IFN-gamma was detected in one patient receiving the highest dose. No changes referable to IFN-gamma inhalation were found in the CL responses of blood neutrophils and monocytes. During the 24 h follow-up, two patients developed transient fever-reactions. CONCLUSIONS: The findings suggest that inhalation may provide a way to increase alveolar concentrations of IFN-gamma and to augment respiratory burst capacity of AM without any major side effects. This approach may have clinical implications for the treatment of tumors and infections of the respiratory tract.

Adult↗
PubMed1995

Evaluation of the clinical TNM staging system for malignant pleural mesothelioma: an assessment in 88 patients.

There is no universally-recognised method for staging malignant mesothelioma, although the use of computed tomograph (CT) scanning has improved the staging of non-invasive disease. The International Union against Cancer has recently proposed using the Tumour Node Metastases (TNM) staging system for mesothelioma, but in clinical practice it is difficult to assess tumour and nodal involvement due to the unique plate-like growth pattern of this tumour. In order to evaluate TNM staging we analysed pre-operative CT scans from 88 patients with histologically-confirmed malignant pleural mesothelioma, all from the same institution. The median age of the patients was 56 years (range 38-79). There were 70 men and 18 women, and 33 had tumours with epithelial histology. The median survival time was 10 months (range 0.2-110), from the date of histological confirmation of mesothelioma. The same radiologist analysed all the CT scans according to the TNM staging system. Actuarial survival curves were constructed by the Kaplan-Meier method. Survival curves for the different TNM categories were compared using the log-rank test. Node evaluation could not be completed in eight cases because the tumour had encompassed the hilum and mediastinum. In multivariate analysis, significant differences in prognosis correlated with the different T categories (P < 0.01), and the different TNM stages (P < 0.05), but not the N categories or the M categories. Larger studies are needed to assess the importance of TNM staging in the selection of treatment and as a prognostic factor for malignant mesothelioma.

Adult↗
PubMed1995

Interferon (IFN)-alpha and IFN-gamma in combination with methotrexate: in vitro sensitivity studies in four human mesothelioma cell lines.

Mesothelioma is a malignant tumor of the serous surfaces in the thorax and abdomen, which has proved exceptionally resistant to treatment. A recent phase II trial of a high-dose methotrexate regime on 63 Norwegian patients has, however, achieved a response rate of 37%. Some responses have also been achieved using interferon (IFN)-gamma administered intrapleurally or recombinant (r) IFN-alpha administered subcutaneously. Our earlier in vitro sensitivity studies of mesothelioma cell lines showed that IFN augments the response to chemotherapeutic agents in mesothelioma. The aim of this study was to assess the response of four mesothelioma cell lines, derived from diffuse asbestos-related pleural malignant mesothelioma, to methotrexate alone and in combination with recombinant IFN-alpha and IFN-gamma. Anti-proliferative effects were assayed by vital dye exclusion. A combination of IFN-alpha and IFN-gamma consistently augmented the response of the cell lines to methotrexate, by as much as 75% for one cell line, although the response to the individual IFNs was variable. We were also able to compare the effects of natural IFN-beta with those of IFN-alpha and IFN-gamma. The IFN-beta sensitivity profile for each of the four cell lines was similar to that of IFN-alpha. In two cell lines, the combination of IFN-beta and IFN-gamma produced a similar effect to the IFN-alpha and IFN-gamma combination.

Drug Interactions↗
PubMed1994

Immunological evidence for co-expression of cluster-5 and cluster-5A small cell lung cancer antigen on a single molecule.

We have investigated immunologically the molecular association of the cell-surface sialoglycoprotein antigens cluster-5 (CL-5) and cluster-5A (CL-5A), known to be co-expressed in human small-cell lung cancer (SCLC). CL-5 antigen is exclusively defined by IgM antibodies as represented by MAb LAM8, whereas CL-5A antigen is exclusively defined by IgG antibodies as represented by MAbs SWA20 and SEN31. Because of the unavailability of purified antigens, the question of the molecular relationship between these antigens was addressed by immunological studies. We generated an anti-anti-idiotypic MAb of the IgG isotype using a CL-5-antigen-mimicking anti-idiotype defined by rat MAb Ly8-229 as an immunogen to circumvent the avidity problems observed with the IgM MAb LAM8 in binding-competition experiments. In addition, we developed a heterologous double antibody sandwich assay able to identify circulating CL-5/5A antigens in pre-treatment sera of patients with SCLC. The results of both types of immunological studies demonstrated the expression of CL-5 and CL-5A antigens on a single molecule, both in cellular assays and in assays detecting antigens shed into the serum of patients with SCLC.

Animals↗
PubMed1994

Absence of trisomy 7 in nonneoplastic human ascitic and pleural fluid cells. An interphase cytogenetic study.

Trisomy 7 is a frequent aneuploid change in lymphomas, adenocarcinomas, and malignant mesenchymal and neurogenic tumors. Moreover, it has been observed in cultured and uncultured non-neoplastic cells from brain, kidney, liver, lung, and atherosclerotic plaques, among other tissues, opening debate on the role of this change in normal and neoplastic tissue. We used nonradioactive in situ hybridization (ISH) with a biotinylated chromosome 7-specific alpha-satellite DNA probe to seek an extra copy of chromosome 7 in ascitic and pleural fluid interphase cells from 26 donors. The donors comprised 24 patients with nonmalignant clinical history, one patient with non-Hodgkin's malignant lymphoma (positive control), and one patient with chronic myeloid leukemia (CML, negative control). The highest frequency of fluid cells with three hybridization signals in patients without neoplasia was 0.5%, in contrast to the frequency of 40.5% noted in the fluid cells of the patient with non-Hodgkin's malignant lymphoma. The results demonstrate that the frequency of trisomic cells in pleural as well as in ascitic fluid is very low, making possible use of the cells in ascitic or pleural fluids in identification of malignancy.

Adult↗
PubMed1994

Normal lung biology.

Explore the source record for details and available documents.

Antineoplastic Agents↗
PubMed1994

Pharmacokinetics and toxicity of inhaled human natural interferon-beta in patients with lung cancer.

Eight patients with a thoracic malignancy inhaled single doses of 3-100 x 10(6) IU of human natural interferon (IFN)-beta via a dosimeter-equipped jet nebulizer. After inhalation IFN-beta was not detectable in any of the serum samples as measured using an antiviral bioassay. Except for a slight body temperature rise and an 18% decrease in peak expiratory flow rate observed in 1 patient the patients did not experience any major side effects. Inhaled natural IFN-beta in this study was tolerated better than inhaled IFN-alpha or IFN-gamma in our previous studies. IFN-beta might thus be a promising local treatment for pulmonary diseases. Further work is needed to investigate the concentrations of biologically active IFN in alveolar epithelial lining fluid after inhalation and the therapeutic effect of inhaled IFN-beta.

Administration, Inhalation↗
PubMed1994

Subcutaneously administered recombinant interferon-gamma in humans: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages, blood neutrophils, and monocytes.

A Phase I trial was conducted to investigate the clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AMs), peripheral blood neutrophils, and monocytes after subcutaneous injection of recombinant interferon-gamma (rIFN-gamma). Six patients with lung cancer received rIFN-gamma subcutaneously as single doses of 0.2, 0.6, and 1.8 mg. Bronchoalveolar lavage was performed three times: 21 h before as well as 6-7 and 27 h after injection. Serum samples were taken five times during the 27-h follow-up. IFN concentrations were measured from alveolar epithelial lining fluid (ELF) and serum by using an antiviral bioassay. IFN-gamma was not detectable in ELF after subcutaneous injection. AMs did not effect an increase in CL responses to N-formyl-methionyl-leucyl-phenylalanine or to phosphate-buffered saline. Circulating IFN-gamma was detectable at 3-12 h after an injection of 1.8 mg of rIFN-gamma, the highest dose given. CL responses of peripheral blood monocytes increased in all patients after injection, whereas the responses of neutrophils were less clear-cut. All patients developed systemic side effects such as transient fever, nausea, headaches, and flu-like symptoms. The findings suggest that rIFN-gamma passes poorly from the blood to the pulmonary alveoli. On the basis of this and our previous findings of increased CL responses in AMs and measurable IFN concentrations in ELF after inhalation of rIFN-gamma, we recommend inhalation rather than the parenteral route of IFN-gamma for the treatment of respiratory diseases.

Adult↗
PubMed1993

Bronchoalveolar lavage fluid findings following radiotherapy for non-small cell lung cancer.

PURPOSE: To evaluate the diagnostic potential of bronchoalveolar lavage fluid analysis in radiation-induced lung injury. METHODS AND MATERIALS: Thirty patients with inoperable non-small cell lung cancer received either high-dose hyperfractionated radiotherapy or radiotherapy and interferon, a potential radiosensitizer, or radiotherapy and N-acetylcysteine, a potential radioprotector. Bronchoalveolar lavages were performed before and immediately after radiotherapy, and thereafter 6-8 weeks and 3 months after radiotherapy. Total and differential cell counts were measured from the bronchoalveolar lavage fluid samples. Urea measured in serum and in bronchoalveolar lavage fluid was used to calculate epithelial lining fluid. The concentrations of protein and phosphatidylcholine, the major surfactant phospholipid, in epithelial lining fluid were measured. The extent of radiation-induced lung injury was assessed from computed tomographies performed before radiotherapy, and 6-8 weeks and 3 months after radiotherapy. RESULTS: More patients in the interferon-arm developed radiation pneumonitis than did patients in the other groups, but no significant differences in alveolar fluid indices were noted between the groups. When all the patients were studied together, radiation was shown to have induced a significant relative increase of lymphocytes in bronchoalveolar lavage fluid 6-8 weeks and 3 months after the end of radiotherapy. The concentration of phosphatidylcholine in epithelial lining fluid decreased significantly 6-8 weeks and 3 months after treatment. The increase in protein concentration in epithelial lining fluid reached a statistically significant level 6-8 weeks after radiotherapy. CONCLUSION: Analysis of bronchoalveolar lavage fluid predicts the degree of radiation pneumonitis; however, radiology remains to be "the gold standard."

Acetylcysteine↗
PubMed1993

Interferon-alpha and interferon-gamma combined with chemotherapy: in vitro sensitivity studies in non-small cell lung cancer cell lines.

Non-small cell lung cancers (NSCLC) are often resistant to chemotherapy. Cisplatin has shown the most activity against all the histological subtypes and is now used in most combined treatment programmes. Interferon (IFN)-alpha has been shown to potentiate cisplatin and other drugs experimentally and in clinical trials involving NSCLC. We are looking at the responses of different NSCLC cell lines to cisplatin (P), etoposide (VP-16) and IFN [recombinant human IFN-alpha 2c (IFN-alpha) and IFN-gamma 1b (IFN-gamma)], individually and in combination. We then compare the results with those from a clinical trial of etoposide and cisplatin with interferon in advanced NSCLC. We report here the results from the first of our cell lines, established from a large cell anaplastic carcinoma. We have confirmed earlier findings that NSCLC cell lines are not sensitive to either IFN-alpha or IFN-gamma alone. However a combination of IFN-alpha and IFN-gamma does reduce cell proliferation in our cell lines. This IFN combination potentiates the response of the cells to etoposide far more than to cisplatin. There is a trend towards greater activity when a combination of cisplatin and etoposide is used, compared with the activity of either drug alone. This effect is further increased by the interferon combination.

Adenocarcinoma↗
PubMed1992

p53 and Kirsten-ras mutations in human mesothelioma cell lines.

Twenty cell lines from 17 individuals with malignant mesothelioma have been examined for p53 alterations by direct sequencing of genomic DNA, by evaluation of mRNA expression levels, and by immunocytochemical analysis of p53 protein expression in comparison with normal human pleural mesothelial cells. The results of this study show p53 abnormalities in cell lines from 3 individuals. These include 2 point mutations and one null cell line. Interestingly, while both cell lines with point mutations exhibit high levels of p53 protein, normal mesothelial cells as well as 12 of the mesotheliomas evaluated express low but significant levels. In addition, sequencing of K-ras at codons 12, 13, and 61 reveals wild-type sequence in all 20 mesothelioma cell lines. The capacity to induce tumors in athymic nude mice did not correlate with the presence of a p53 mutation or elevated p53 protein levels. These data suggest that neither p53 alteration nor K-ras activation constitutes a critical step in the development of human mesothelioma.

Animals↗
PubMed1992

Abnormalities of chromosomes 7 and 22 in human malignant pleural mesothelioma: correlation between Southern blot and cytogenetic analyses.

Southern blot hybridization studies were performed on 23 mesothelioma primary tumor specimens to detect chromosome 1-, 7-, and 22-specific numerical changes, gene amplifications, and gene rearrangements. The molecular findings were compared with previous cytogenetic findings. No gene rearrangements or amplifications were detected. A numerical abnormality of chromosome 7 was detected by Southern blot analysis in two cases in which no numerical abnormality had been detected by the previous chromosome study. A numerical aberration of chromosome 22 was detected in five cases, which was compatible with the cytogenetic finding of monosomy 22 in these cases. The Southern blot results for the copy numbers of chromosomes 7 and 22 were concordant with the cytogenetic findings in 65%-80% of the cases.

Blotting, Southern↗
PubMed1992

Chromosome number correlates with survival in patients with malignant pleural mesothelioma.

Modal (MO) and mean (ME) chromosome numbers determined by cytogenetic analysis were compared with survival in 34 patients with diffuse malignant pleural mesothelioma. The patients with normal chromosome number and no clonal abnormalities (MO = 46) survived longer (median survival 17 months) than patients with clonal abnormalities. MO greater than 46 correlated with shorter survival (median 12 months) (p = 0.0186). The correlation was more clear between mean chromosome number (ME) and survival: the median survival of patients with ME greater than 46 was 13 months whereas that of the patients with ME less than 46 was 26 months and ME = 46 (normal chromosome number and no clonal abnormalities) 31 months (p = 0.0007). Furthermore, there was a tendency of an association between ME = 46, ME less than 46 and epithelial subtype reported to be associated with a favorable prognosis in mesothelioma. The addition of chromosome material may present a mechanism to enhance expression of genes important in the pathogenesis of mesothelioma and lead to more aggressive behavior of the tumor.

Chromosome Aberrations↗